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Portal vein embolization and colorectal liver metastases
Eric Vibert, MD, PhD
Centre Hépato-Biliaire
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Plan
• Why we perform Portal Vein Occlusion ?
• How we perform Portal Vein Occlusion ?
• What are the consequences of PVE on
– Fonction ?
– Volume ?
– Histology of the liver ?
– Tumor ?
• Alternative to PVE ?
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To avoid post-operative liver failure
< 20% of standard liver volume or 0.5% body weight
Liver SP Liver SP
Truant et al. JACS 2008Ribeiro, Vauthey et al. BJS 2007
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No liver resection with a liver remnant volume < 0.5% of body weight ratio
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2011
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MHV
RHV
Vcongestion
NCLR : 29%
NCLR : 20%
Vascular reconstructionMise et al. BJS 2011
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The middle hepatic vein is betweenthe right and the left liver…
Be careful to liver resection that cut middle hepatic vein
« Morphological » Vol. ≠ « Functional » Vol.
Tanaka et al. Surgery 2010
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?
Pas de veine hépatique inf. droite
Foie gauche = 0,5%
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Interhepatic vein anastomoses
e flow
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Post-hepatectomy liver failure
At D3 et/ou D5 : Bilirubine > 50 µMol/L and TP < 50% 50 à 63% of 1 month mortality
50
J5
De J1 et J90 : Bilirubine > 120 µMol/L 70% of 3 month mortality
Balzan…Belghit et al. Ann Surg 2005 Paugam…Belghit et al. Ann Surg 2009 Mullen…Vauthey et al. JACS 2007
And /Or
n=1057 majors hepatectomies
in non cirrhotic liver
n=870 then n=436
hepatectomies
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2011
Gp A
Gp B
Gp C
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Post-operative liver failure is the consequence of macroscopic and
microscopic liver « desorganization »
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Difference between fulminant hepatitis and major hepatectomy
Fulminant hepatitis Major hepatectomy
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« The liver is not a Brocoli, it is 2 Brocolis »
INFLOW OUTFLOW
Sano et al,, Ann Surg 2002
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The liver function is related to vascular surface between hepatocytes / sinusoids
Hoelme et al. PNAS 2010
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Day 0 Day 4
Hepatocytes
proliferationEndothelial
proliferation
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Before hepatectomy
Day 0 to Day 4 / major hepatectomy
Hepatocytes multiplication +++
Œdema Increase of portal pressure
Decrease of exchange surface between endoth. cell and hepatocytes Poor liver function
After Day 4 / major hepatectomy
Improve of « liver permeability »
Endothelial prolifération +++
Enlargment of surface exchange between LSEC and Hep. Function
PV
CLVHepatocytes
Endothelial Cell
Biliary cell
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Patients and MethodsPortal Vein Pressure measurement
• When? 30 min to 1 hour after liver transection just before abdominal closure
• How? Transducer connected to a 25 gauge needle inserted into the portal trunk
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There is a correlation of PVP with liver failure and 90-day mortality
YesNoPost
hep
atec
tom
y P
VP
(m
mH
g)
22.5 mmHg
15 mmHg
P < 0.001
Liver failure « 50-50 » criteria 90-day mortality
YesNo
15 mmHg
19 mmHg
P = 0.01
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Optimal cutoff of PVP for each liver failure definition
« 50-50 » criteria Peak of serum bilirubin > 7 mg/dL
ISGLS grade 3 definition
22 mmHg 22 mmHg21 mmHg
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Incidence of POLF after
hepatectomy for CRLM
Auteur Date Période Hépatectomie Mortalité po Hep.Maj Ins.Hep Ins.Hep/Maj.
N. % N. % %
Figueras et al. 2001 1991-2000 256 4,0 145 0,8 1,4
Tamandl et al. 2007 2001-2004 276 0,0 27 0,7 7,4
Finch et al. 2007 1993-2003 484 3,5 349 0,4 0,6
Gold 2008 1992-2003 443 2,9 380 0,5 0,5
Mehta 2008 2003-2005 173 4,0 127 1,2 1,6
Welsh et al. 2008 1987-2005 911 1,5 0,2
Kesmodel 2008 2004-2006 125 1,6 (3 mois) 77 1,6 2,6
Konopke 2009 1993-2008 107 0,9 49 1,9 4,1
Ferrero 2010 2002-2004 80 0,0 39 2,5 5,1
Schiesser 2008 1992-2005 197 2,5 126 1,0 1,6
Karanjia et al. 2008 1996-2006 283 2,1 151 0,7 1,3
2,1% 1% 2,6%
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96
10
26
114
00
20
40
60
80
100
120
Grade 0 Grade 1 Grade 2 Grade 3 Grade 4 Grade 5
34
6
22
14
7
2
0
5
10
15
20
25
30
35
40
Grade 0 Grade 1 Grade 2 Grade 3 Grade 4 Grade 5
147 Hépatectomies mineures
85 Hépatectomies majeures
32% Gr 1-2 27% Gr 3-4-5
24% Gr 1-2 11% Gr 3-4-5
Morbidité 33% Mortalité 0%
Morbidité 59% Mortalité 2%
Morbidité grave
Morbidité grave
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Maj + Min Mineure (<3 seg) Majeure (>2 seg) p
N=232 N=147 N=85N(%) or Moy±SD N(%) or Moy±SD N(%) or Moy±SD
Insuff. hép. post hep. 7 (3%) 1 (0,8%) 6 (7%) 0,002
Fistule Biliaire 19 (8) 11 (7) 8 (9) 0,04Ascite 17 (7) 3 (2) 14 (16) 0,0001Pneumopathie 15 (6) 9 (6) 6 (6) 0,77Confusion mentale 14 (6) 4 (3) 10 (11) 0,005Infection urinaire 12 (5) 6 (4) 6 (7) 0,32Collection péri-hépatique infecté
9 (4) 2 (1)7 (8) 0,009
Hémorragie 6 (2) 3 (2) 3 (3) 0,49Thrombose portale 2 (1) 0 2 (2) 0,06
Hospit. en Réanimation (jours) 2,3±3,3 1,8±2,3 3,1±4,5 0,007Hospitalisation globale (jours) 13,3±24 12,3±30,4 14,2±8,7 0,58
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Toutes Hépatectomies(N=232)
Hépatectomies majeures (N=85)
RR (95% CI) p RR (95% CI) p
PO. Liver Failure 3,84 (1,01 – 14,4) 0,04 4,14 (1,29 – 14,8) 0,01
Mental Confusion 3,11 (1,37 – 7,14) 0,006 3,66 (1,18 – 12,5) 0,02
Infected Collection 2,87 (1,24 – 6,62) 0,01 -
Intraop Transf. 2,27 (1,21 – 4,09) 0,009 -
1er pronostic factor of long
term mortality after hep. for
colorectal liver met.
PO. Liver FailureSuivi moy. > 36 mois
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C.H.B
J Am Coll Surg 1995; 181
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C.H.B
Portal Puncture Under US Controle
Left Portal Branch
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C.H.B
Right Portal Vein Embolization
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C.H.B
Anatomical Hepatectomy after Fonctional Hepatectomy
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2007
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1 weeks
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PVE allows to operate patient with finally the same overall result
2000
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P=0.004
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1995
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2001
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2009
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2012
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87 pts with PVE and chemotherapy to be operated
47 Slow responders : > 12 cycles of chemo.
40 Fast responders : < 12 cycles of chemo.
2012
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PVE and chemo…
2008
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Injection de cellule tumorale en intra splénique ou systémique et procédure à J7
In the liverIn the chest
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Subcapsular hepatoma in rat thenlaparotomy, hep 30% or hep 60%
Evolution of the tumor ?
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PV Ligation + In situ Splitting
« ALPPS » for Associated Liver Partition and Portal ligation for Staged hepatectomy
+ 72% in 9 days…
N=25
2012
To win time and volume….
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The Solution to prevent small remnant liver ?
Or a dangerous method to explore with caution ?
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Conclusion
• Portal vein embolization allows to decrease to the risk ofpo. Liver failure after major hepatectomy for colorectal livermetastasis
• Portal vein embolization increases the growth of colorectalliver metastases– Short term period between PVE / Hepatectomy– PVE and chemotherapy
• Alternative to PVE must be explored…– Major hepactomy seems did not increased malignancy– Portal flow modulation to prevent po. Failure with PVE
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The future… Removable AdjustableVascular Ring around the portal vein